Hauwaerts (Celyad): By the time the IND is filed and companies start treating in humans, they must be able to describe all manufacturing processes and materials in sufficient detail. In addition, development cycles in the clinic for CAT companies can be fast, so companies often need to develop manufacturing quickly. Into Phase I and definitely by Phase II, CAT companies need to make definitive choices related to manufacturing. To be able to do so, they also need a clear view about their indication, the size of their target patient population, and the way the product will be used in the hospital environment.
Grant (Invetech): By Phase I, companies should consider development of a manufacturing planning document that presents an initial outline of the path forward to full capacity. This should identify all of the production processes and the technologies available to execute them. The plan should also indicate where investments in equipment will be necessary in the development timeline.
Hauwaerts (Celyad): By Phase II, feedback from regulators related to manufacturing is key, and this is where they tend to get very involved. Initially their feedback is on safety, focusing on issues such as viral banks, raw materials and sera. At later stages, feedback tends to focus on product potency and consistency/variability. Guidelines and standards for advanced therapy medicinal products (ATMPs) are out there, and regulators do expect CAT companies to adhere to them. Regulators are well educated, and know what is achievable in manufacturing and testing, but they look to the CAT companies to come up with the solutions for their specific products.
Grant (Invetech): Phase II is when CAT companies really have to lock in and invest in their manufacturing process. They need to move toward commercial scale even though they don’t need to be 100 percent there yet.